ArticleAutophagy2019
A family of PIKFYVE inhibitors with therapeutic potential against autophagy-dependent cancer cells disrupt multiple events in lysosome homeostasis.
Article in Autophagy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
83 citing papers in PubMed, 1 synthesis or guideline pooled it, 131 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Facile synthesis of amorphous coordinated metal-drug frameworks for cancer immunotherapy.Materials today. Bio · 2026Article
- Targeting PIKfyve: Chemical Biology and Drug Discovery Insights.Chemical biology & drug design · 2026Review
- PI4K and PIPK families in breast cancer: subtype-specific oncogenic mechanisms and precision therapeutic strategies.Molecular biology reports · 2026Review
- Targeting lysosome-dependent cell death in cancer: towards therapeutic strategies.Biomarker research · 2026Review
- Fatty acid synthesis therapy-induced senescence (FASTIS) in cancer cells.Cell death & disease · 2026Article
- How endosomal PIKfyve inhibition prevents viral membrane fusion and entry.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- PIP5K3 upregulation correlates with unfavorable prognosis in patients with nasopharyngeal carcinoma.Histology and histopathology · 2026Article
- Targeting IPNature communications · 2026Article
- PIKfyve mediates the maturation of mycobacteria-containing vesicles.Frontiers in cellular and infection microbiology · 2026Article
- In silico discovery and experimental validation of natural derivatives as inhibitor of phosphoinositide Kinase, PIKfyve.Journal of computer-aided molecular design · 2025Article
- Lysosomal swelling triggers LRRK2 activity.bioRxiv : the preprint server for biology · 2025Article
- How endosomal PIKfyve inhibition prevents viral membrane fusion and entry.bioRxiv : the preprint server for biology · 2025Article
- Mechanism of phosphoinositide regulation of lysosomal pH via inhibition of CLC-7.bioRxiv : the preprint server for biology · 2025Article
- BLOC-1 and BORC: Complex regulators of endolysosomal dynamics.Cell chemical biology · 2025Review
- Structure-Activity Relationship Study of 3-Alkynyl-6-aryl-isothiazolo[4,3-Pharmaceuticals (Basel, Switzerland) · 2025Article
- Spatio-temporal processes in autophagosome-lysosome fusion.Medical review (2021) · 2025Review
- PIP4K2C inhibition reverses autophagic flux impairment induced by SARS-CoV-2.Nature communications · 2025Article
- An advanced toolset to manipulate and monitor subcellular phosphatidylinositol 3,5-bisphosphate.The Journal of cell biology · 2025Article
- Phosphoinositide kinases in cancer: from molecular mechanisms to therapeutic opportunities.Nature reviews. Cancer · 2025Review
23 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
High-throughput screening identified 5 chemical analogs (termed the WX8-family) that disrupted 3 events in lysosome homeostasis: (1) lysosome fission via tubulation without preventing homotypic lysosome fusion; (2) trafficking of molecules into lysosomes without altering lysosomal acidity, and (3) heterotypic fusion between lysosomes and autophagosomes. Remarkably, these compounds did not prevent homotypic fusion between lysosomes, despite the fact that homotypic fusion required some of the same machinery essential for heterotypic fusion. These effects varied 400-fold among WX8-family members, were time and concentration dependent, reversible, and resulted primarily from their ability to bind specifically to the PIKFYVE phosphoinositide kinase. The ability of the WX8-family to prevent lysosomes from participating in macroautophagy/autophagy suggested they have therapeutic potential in treating autophagy-dependent diseases. In fact, the most potent family member (WX8) was 100-times more lethal to 'autophagy-addicted' melanoma A375 cells than the lysosomal inhibitors hydroxychloroquine and chloroquine. In contrast, cells that were insensitive to hydroxychloroquine and chloroquine were also insensitive to WX8. Therefore, the WX8-family of PIKFYVE inhibitors provides a basis for developing drugs that could selectively kill autophagy-dependent cancer cells, as well as increasing the effectiveness of established anti-cancer therapies through combinatorial treatments.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.